Project description:To identify molecular characteristics of young and aged lungs post-influenza infection, we isolated RNA from lungs 60 days post-infection and examined by bulk RNAseq. We found a large number of genes remain upregulated in aged compared to young lungs. Comparison with expression of immune system-related genes from Nanostring expriments indicated this was largely infection-induced rather than baseline differences between age. This indicates that aged lungs fail to return to homeostasis following a viral respiratory infection
Project description:Seasonal influenza causes significant morbidity and mortality worldwide, with 70-90% of these deaths occurring in individuals aged 65 or older. To explore the mechanisms behind this age-related vulnerability, we investigated immune responses and inflammation in the lungs of young and old mice during influenza A virus (IAV) infection. Young (12-week) and old (70-week) C57BL/6J mice were intranasally infected with IAV PR8, and immune responses were assessed at 7 days post-infection (dpi) using single-cell RNA sequencing (scRNA-seq).
Project description:Aging is known to alter the host repsonse to influenza infection. Here, we use single-cell RNA sequencing (scRNA-seq) to identify cellular changes in the lungs of young (16-week-old) and aged (80-week-old) mice following influenza infection.
Project description:Aging is known to alter the host repsonse to influenza infection. Here, we use bulk RNA sequencing (bulk RNA-seq) to identify cellular changes in the lungs of young (16-week-old) and aged (80-week-old) mice following influenza infection.
Project description:Aging is known to alter the host repsonse to influenza infection. Here, we use 10x Visium spatial sequencing to identify spatial changes in mRNA expression of left lungs of young (16-week-old) and aged (80-week-old) mice following influenza infection.
Project description:Project investigates lung extracellular matrix recovery after influenza infection. Influenza A strain APR8 was adminsitered intranasally. Infection caused transient weight loss which fully recovered by day 12. On day 21 post-infection (when mice were asymptomatic and fully recovered) lungs were harvested and compared to control non-infected by LC-MS/MS.
Project description:Purpose of this experiment was to study the host-transcriptional response to MA-15, MA-15epsilon, and MA-15-gamma in both young and aged mice to further understand the differences between response within each age group, and the age-related differences in response to each virus. Young (8 weeks old) and aged (1 year old) female BALB/c mice were intranasally infected with 10^5 PFU of either MA15, MA15 gamma, MA15 epsilon, or phosphate buffer solution (PBS; mock-infection). Lungs from aged mice were harvested at 12, 24, and 48 hours post-infection. Lungs from young mice were harvested at 12, 24, 48, and 96 hours post-infection. For the aged mice, 3 biological replicates were collected for microarray analysis at each time point from the infected groups. 3 mocks at 12h, 2 mocks each at 24 and 48h time points.For the young mice, 4 biological replicates were collected for microarray analysis at each time point from the infected groups.
Project description:To identify molecular characteristics of lung tissue from WT mice treated with DMSO or a new insulin sensitizer MSDC-0602K at day 4 post influenza virus infection, we isolated RNA from lungs with various treatments and examined by bulk RNA-seq. We found a large number of gene profiles were altered following MSDC-0602K treatment in lungs. Interestingly, gene sets involved inflammatory responses were enriched in DMSO treatd mouse lungs whereas gene set of fatty acid metabolism was enriched in MSDC-0602K treated mouse lung, suggesting MSDC-0602K treatment diminshed pulmonary inflammation and altered metabolic status during influenza virus infection.
Project description:In June 2009, the World Health Organization declared the first influenza pandemic of the 21st century, due to the emergence and rapid spread of new swine origin H1N1 influenza A virus. In contrast to seasonal influenza infections, which typically cause morbidity and mortality in the elderly, this virus caused severe infection in young adults and not the elderly. This phenomenon was attributed to the presence of cross-neutralizing antibodies acquired by older individuals from previous exposure to swine origin influenza. However, this hypothesis could not be empirically tested using clinical data. To address this question, we investigated viral replication and the development of the immune response in naï12 years old) and aged (20 to 24 years old) female rhesus macaques infected with A/California/04/2009 (H1N1), one of the circulating pandemic strains in 2009. We compared viral loads as well as the kinetics and magnitude of the adaptive immune response in peripheral blood and bronchoalveolar lavage samples (BAL) collected longitudinally for 99 days post-infection. Although, adult animals exhibited earlier T cell responses in peripheral blood, aged animals generated a robust T cell response with comparable kinetics and magnitude as those observed in young animals in BAL. Moreover, aged animals generated a higher hemagglutination inhibition titer compared to young animals. We also measured the concentration of several cytokines in BAL supernatant. With the exception of IL-8, which was higher in aged animals, we found no differences in IFNa, IFNb, TNFa, IL-1r, IL-6, IL-15, IL-17, or MCP1 levels. Finally, we compared gene expression infection using microarray analysis of BAL samples taken on days 0, 4, 7, 10, and 14 pi. Our analyses revealed that the largest difference in host response between aged and young animals was detected day 4 post-infection, with significant enrichment for genes associated with inflammation, the innate immune response, and T cell activation in aged animals. The ability of aged animals to generate a robust immune response, especially antibody response, following infection with 2009 H1N1 virus could explain the lack of morbidity normally observed with seasonal influenza viruses in this vulnerable population. 16 female rhesus macaques (Macaca Mulatta) 10-12 (Adult) and 20-24 years (Old/Aged) of age were used in these studies. Animals were infected with A/California/04/ 2009 H1N1 using a combinatory of intra-tracheal (4ml), intranasal (0.5 ml/nostril), and conjunctival (0.5 ml/eyelid) routes for a total dose of 7x106 TCID50 dose. Microarray analysis was performed on Bronchoalveolar lavage (BAL) samples collected on days 0, 4, 7, 10 and 14. Note: One of the Day 0 array did not pass QC metrics so for this animal the average of the other Day 0 samples from that group was utilized. At the end of the study animals were released back to the colony.
Project description:To identify molecular characteristics of lung tissue from db/db mice treated with DMSO or a new insulin sensitizer MSDC-0602K at day 5 post influenza virus infection, we isolated RNA from lungs with various treatments and examined by bulk RNA-seq. We found a large number of gene profiles were altered following MSDC-0602K treatment in lungs. Interestingly, a number of genes accounting for pulmonary inflammatory responses were significantly decreased following MSDC-0602K treatment in lungs of db/db mice at day 5 post influenza virus infection. Moreover, MSDC-0602K treated lung tissue showed lower levels of genes related to glucose metabolism.